Changes in the mucus barrier of the rat during 5-fluorouracil-induced gastrointestinal mucositis.
OBJECTIVE
A frequent complication of antineoplastic chemotherapy (CT) is gastrointestinal (GI) mucositis. Although clinically this mucositis can be treated, data on the effect of CTon the mucosal defense mechanisms are scant, so the effects of 5-fluorouracil (5-FU) on mucin, one of the principal defense factors of the GI mucosa, were investigated.


METHODS
5-FU was administered orally to rats at a dose of 50 mg/kg once daily for 5 days. Using anti-mucin monoclonal antibodies, the immunoreactivity in different areas of the rats' GI tracts was compared, as well as the mucin content. Changes in the GI mucin during the process of recovery from the injury were also investigated. Immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) was used to determine whether or not the effects of 5-FU on cell proliferation contributed to the changes in mucin.


RESULTS
5-FU caused significant alterations of the immunoreactivity and content of mucin in the rat GI mucosa, especially in the jejunum. The jejunal mucin content was most markedly reduced on day 1 after drug withdrawal, and increased thereafter. By day 7, the content had transiently but significantly increased approximately 1.5-fold, and returned to the basal level by day 13. The number of PCNA-positive cells strikingly decreased at day 1, but by day 7 had increased approximately 2-fold, compared with the control.


CONCLUSIONS
The activation of mucus cells in the jejunum, if appropriately manipulated, could lead to more effective prevention of CT-induced GI mucositis.
Saegusa
Yoichi
Y
Department of Internal Medicine, Kitasato University Graduate School of Medicine, Sagamihara, Kanagawa, Japan.
Ichikawa
Takafumi
T
Iwai
Tomohisa
T
Goso
Yukinobu
Y
Okayasu
Isao
I
Ikezawa
Tomoaki
T
Shikama
Nobuaki
N
Saigenji
Katsunori
K
Ishihara
Kazuhiko
K
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D007150:Immunohistochemistry; D007583:Jejunum / Q000187:drug effects; D008297:Male; D009077:Mucins / Q000032:analysis; D052016:Mucositis / Q000139:chemically induced*; D009093:Mucus / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D009077:Mucins; D005472:Fluorouracil